Details

Autor(en) / Beteiligte

• Talmadge E. King, Jr
• Sharon Safrin
• Karen M. Starko
• Kevin K. Brown
• Paul W. Noble
• Ganesh Raghu
• David A. Schwartz

Titel

Analyses of Efficacy End Points in a Controlled Trial of Interferon-γ1b for Idiopathic Pulmonary Fibrosis

Ist Teil von

• Chest, 2005-01, Vol.127 (1), p.171

Ort / Verlag

American College of Chest Physicians

Erscheinungsjahr

2005

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Background: Idiopathic pulmonary fibrosis (IPF) is a devastating disease, yet validated, reliable criteria for evaluating patient response to therapies in clinical trials are lacking. Methods: To optimize selection of end point criteria for the study of interferon (IFN)-γ1b in patients with IPF, we retrospectively analyzed the components of the primary efficacy end point used in a large, controlled study of 330 patients for reliability, validity, and sensitivity to treatment effect. The primary end point components were death, disease progression defined as a ≥ 5 mm Hg increase in resting alveolar-arterial oxygen pressure gradient (P[A-a]O 2 ), and disease progression defined as a ≥ 10% decrease in percentage of predicted FVC. Results: We found that the P(A-a)O 2 criterion was not reliable and was not associated with mortality. In contrast, the FVC criterion was reliable and was associated with a 2.4-fold increase in the risk of death. Of the three measures, only mortality was sensitive to a treatment effect of IFN-γ1b. Additionally, the tendency for mortality benefit was observed in nearly all patient subgroups defined by baseline physiology. The effect of IFN-γ1b on mortality was strongest in patients with baseline percentage of predicted FVC ≥ 55% (p = 0.004) or percentage of predicted diffusing capacity of the lung for carbon monoxide ≥ 30% (p = 0.008). Conclusion: We conclude that mortality is the most inclusive end point for future trials of IFN- γ1b in patients with IPF, and that a > 10% decrement in the percentage of predicted FVC represents a valid measure of disease progression.